Performance of the Xpert MTB/RIF assay in the diagnosis of tuberculosis in formalin-fixed, paraffin-embedded tissues.

Department of Biomedical Sciences, University of School of Medicine, Lusaka, Zambia.

2

University of and University College London Medical School (UNZA-UCLMS) Research and Training Programme, University Teaching Hospital, Lusaka, Zambia.

3

Department of Pathology and Microbiology, University Teaching Hospital, Lusaka, Zambia.

4

University of Zambia and University College London Medical School (UNZA-UCLMS) Research and Training Programme, University Teaching Hospital; Institute for Infectious Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

5

Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

6

National TB and Leprosy Control Programme, Ministry of Community Development, Mother and Child Health, Lusaka, Zambia.

7

Department of Infection, Division of Infection and Immunity, University College London; National Institute for Health Research Biomedical Research Centre at UCL Hospitals, London, United Kingdom.

Abstract

OBJECTIVE/BACKGROUND:

Extrapulmonary tuberculosis (EPTB), which accounts for 10%-40% of the global burden of TB, with the highest incidence in Sub-Saharan Africa, is strongly associated with human immunodeficiency virus infection. Diagnosing EPTB is challenging, and recently, there has been a concerted effort to evaluate the latest molecular diagnostics for diagnosing TB in a range of specimen types. The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) is one such technology, which simultaneously detects Mycobacterium tuberculosis and rifampicin resistance. Our objective was to evaluate the accuracy of the Xpert MTB/RIF assay for the diagnosis of EPTB and detection of rifampicin resistance in routinely processed formalin-fixed, paraffin-embedded (FFPE) tissues, compared with histological detection of TB as the gold standard.

RESULTS:

Some 66% of specimens had histological evidence of TB infection. ZN staining was positive for TB in 8% of cases, and Xpert MTB/RIF was positive for TB in 25% of cases. Taking histology as the gold standard, the sensitivity and specificity were as follows: In lymph tissue the accuracy of the Xpert MTB/RIF assay was 41% (95%CI 27-57), not significantly better than ZN or the in-house PCR assay. In non-lymph tissue the sensitivity of the in-house PCR assay was 82% (95%CI: 56%-95%), significantly higher than the Xpert MTB/RIF assay (P = 0.004). The Xpert MTB/RIF assay indicated rifampicin resistance in just three cases.

CONCLUSION:

The Xpert MTB/RIF assay is potentially a useful tool for the diagnosis of TB in routine FFPE tissues.